This application requests funding for a four-year study to investigate psychophysiological markers for substance abuse in children ages 13-17 who are at high risk for substance abuse by virtue of their parental history for this condition. The rationale for the present proposal is to search for psychophysiological abnormalities associated with the two main dimensions of personality linked to substance abuse, that is, negative affectivity/anxiety and disinhibited/antisocial behaviors. Theorists have proposed a biobehavioral model based on responses to aversive and appetitive stimuli to explain the neurophysiological basis of motivational behaviors and to account for childhood mental disorders. The model posits that motivational behaviors is influenced by an arousal system, and by a behavioral inhibition system (BIS), which processes signals related to aversive stimuli, and a behavioral activation system (BAS), which processes signal related to rewards. Psychopathology is assumed to result from an imbalance within these systems. The major hypothesis for which we have preliminary support is that distinct deficits in arousal and/or affective responses underlie the relationship between substance abuse and both anxiety and disinhibited/antisocial personality. Specifically we will examine the following in children of parents with 1) substance abuse only, 2) substance abuse and comorbid anxiety disorder, 3) substance abuse and antisocial personality disorder, and 3) no psychiatric disorders: 1. startle potentiation and autonomic nervous system (ANS) measures of arousal to threat of aversive stimuli; 2. ANS responses to reward and to the removal of reward; 3. Asymmetry of resting EEG; 4. the association between psychophysiological measures of BAS and BIS activity and temperamental characteristics associated with anxiety and disinhibited/antisocial behavior; 5. the effects of the gender of the offspring in the relationship between parental history and the offspring's psychophysiological, temperamental, and clinical characteristics; 6. phenotypic indices of vulnerability using combinations of clinical and psychophysiological measures.